Journal article
Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma: A Unique Case With Morphologic, Immunohistochemical, and Genomic Characterization
Medicine (Baltimore), Vol.93(15), pp.e81-e81
10/01/2014
DOI: 10.1097/MD.0000000000000081
PMID: 25275525
Abstract
Renal oncocytoma is a benign tumor with characteristic histologic findings. We describe an oncocytoma-like renal tumor with progression to high-grade oncocytic carcinoma and metastasis.
A 74-year-old man with no family history of cancer presented with hematuria. Computed tomography showed an 11 cm heterogeneous multilobulated mass in the right kidney lower pole, enlarged aortocaval lymph nodes, and multiple lung nodules. In the nephrectomy specimen, approximately one third of the renal tumor histologically showed regions classic for benign oncocytoma transitioning to regions of high-grade carcinoma without sharp demarcation.
With extensive genomic investigation using single nucleotide polymorphism-based array virtual karyotyping, multiregion sequencing, and expression array analysis, we were able to show a common lineage between the benign oncocytoma and high-grade oncocytic carcinoma regions in the tumor. We were also able to show karyotypic differences underlying this progression. The benign oncocytoma showed no chromosomal aberrations, whereas the high-grade oncocytic carcinoma showed loss of the 17p region housing FLCN (folliculin [Birt–Hogg–Dubé protein]), loss of 8p, and gain of 8q. Gene expression patterns supported dysregulation and activation of phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (Akt), mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK), and mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathways in the high-grade oncocytic carcinoma regions. This was partly attributable to FLCN underexpression but further accentuated by overexpression of numerous genes on 8q. In the high-grade oncocytic carcinoma region, vascular endothelial growth factor A along with metalloproteinases matrix metallopeptidase 9 and matrix metallopeptidase 12 were overexpressed, facilitating angiogenesis and invasiveness.
Genetic molecular testing provided evidence for the development of an aggressive oncocytic carcinoma from an oncocytoma, leading to aggressive targeted treatment but eventual death 39 months after the diagnosis.
Details
- Title: Subtitle
- Oncocytoma-Like Renal Tumor With Transformation Toward High-Grade Oncocytic Carcinoma: A Unique Case With Morphologic, Immunohistochemical, and Genomic Characterization
- Creators
- Sahussapont J Sirintrapun - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Kim R Geisinger - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Adela Cimic - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Anthony Snow - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Jill Hagenkord - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Federico Monzon - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Benjamin L Legendre - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Anatole Ghazalpour - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Ryan P Bender - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)Zoran Gatalica - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (SJS); University of Mississippi Medical Center, Jackson, MS (KRG); Department of Pathology, Wake Forest Baptist Health, Winston-Salem, NC (AC, AS); 23andMe, Mountain View (JH); Invitae, San Francisco (FM), CA; Transgenomic (BLL); Creighton University School of Medicine (ZG), Omaha, NE; and Caris Life Sciences, Phoenix, AZ (AG, RPB, ZG)
- Resource Type
- Journal article
- Publication Details
- Medicine (Baltimore), Vol.93(15), pp.e81-e81
- DOI
- 10.1097/MD.0000000000000081
- PMID
- 25275525
- NLM abbreviation
- Medicine (Baltimore)
- ISSN
- 0025-7974
- eISSN
- 1536-5964
- Publisher
- Wolters Kluwer Health
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984047898202771
Metrics
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